1. Field of the Invention
This invention generally relates to the field of delivery vehicles for use in diagnostic and therapeutic applications, and specifically towards diagnostic and therapeutic applications involving hypoxic areas of a patient.
2. Description of Related Art
Hypoxic tissue areas are defined as areas having low oxygen content. Generally, the hypoxic tissue area is a result of numerous factors including, but not limited to, a reduction of the oxygen-carrying capacity of blood as a result of a decrease in the total hemoglobin or an alteration of the hemoglobin constituents, decreased blood flow, and any abnormal cellular growth. As a result of the decreased oxygen content, the hypoxic areas are further characterized as having increased tonicity, and a low pH due to acid build-up resulting from anaerobic glycolosis.
Hypoxic areas occur anywhere in the body of a patient, but are particularly found in areas associated with injuries occurring as a result of a stroke, decreased blood flow, reperfusion injury, decreased vascular development, and tumors. With regard to tumors, experiments have provided direct and indirect evidence of hypoxic areas occurring in tumors therein. For example, tests involving glass polarographic electrodes confirm the presence of hypoxia in tumors.
Hypoxic areas located within regions of a tumor are of particular concern to researchers involved with tumor and cancer treatment. Low oxygen levels within regions of a tumor or cancer limits the effectiveness of radiation therapy, since cells maintained in a hypoxic environment are resistant to radiation damage. Radiation resistance occurs because free radicals produced in the presence of low oxygen levels are less damaging toward tumor cells. Consequently, more treatment is required in these hypoxic areas in order to kill the tumor cells.
Generally, in order to treat tumors, the tumor regions must first be found and then targeted. Presently, there is no routine technique available to target tumor tissue. More importantly, no routine clinical tool is available specifically applicable towards imaging tumor hypoxia and to deliver treatment directly thereto.
A number of techniques to monitor tumor hypoxia are available or are under development. These techniques include glass polarographic assay, alkaline comet assay, nitroimidizole-related radiolabelled compounds (Zhang et al. 1998), and fluorine-MRI using hexofluorobenzene. The most widely used measurement of tumor hypoxia is the glass electrode technique. The limitations of this technique however, are that measurements do not adequately represent the entire tumor, since measurements are limited to tissue oxygenation along a linear tract, 1 or 2 mm deep.
Other techniques for measuring tumor hypoxia include NMR of fluorinated compounds (Mason et al. 1998) and techniques based on oxygen quenching of the fluorescence of an excited fluorophor immobilized in a polymer at the end of an optical fiber (Young et al. 1996). The inherent problem with these techniques is that they all require tumor access and are highly invasive. On the other hand, techniques that are non-invasive, such as imaging techniques using nitroimidazole analogues, yield only relative values of tissue oxygen since binding intensity is affected by tumor metabolism.
Accordingly, there is a need for a non-invasive, accurate and detectable mechanism for determining the location of hypoxic areas, and specifically hypoxic areas associated with tumors. Moreover, there is a need for a method of diagnosing and therapeutically treating hypoxic areas associated with tumors. Additionally, there is a need for a routine, non-invasive measurement of human tumor hypoxia in order to determine the effectiveness of chemotherapy as well as radiation therapy. Further, there is a need for improving standard radiation therapy by targeting the small radiation resistant hypoxic regions of a tumor.